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IKONOS imagery has been used in many commercial, government, and research applications ranging from environment monitoring, to coastal change detection, and to national security. The high costs of IKONOS high end products ͑Pro and Precision products͒ make it extremely attractive to find practical methods that use lower-cost IKONOS Geo products to produce highly accurate mapping products. This paper presents four different models defined in both object space and image space to refine the rational function derived ground coordinates. The models are the translation, scale and translation, affine, and second-order polynomial models. Different configurations of ground control points ͑GCPs͒ are carefully examined to evaluate the impact on accuracy improvement. The models are tested based on two IKONOS stereo pairs acquired in the Lake Erie coastal area. It is demonstrated that if an appropriate model and GCPs are used, ground point errors can be reduced from 5-6 to 1.5 m in horizontal and from 7 to 2 m in vertical directions.

A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota–host cross-talk. We developed an enzyme activity–screening platform to investigate how gut microbiota–derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.

Presenilins (PS) are thought to contain the active site for presenilinase endoproteolysis of PS and c-secretase cleavage of substrates. The structural requirements for PS incorporation into the c-secretase enzyme complex, complex stability and maturation, and appropriate presenilinase and c-secretase activity are poorly understood. We used rescue assays to identify sequences in transmembrane domain one (TM1) of PS1 required to support presenilinase and c-secretase activities. Swap mutations identified an N-terminal TM1 domain that is important for c-secretase activity only and a C-terminal TM1 domain that is essential for both presenilinase and c-secretase activities. Exchange of residues 95-98 of PS1 (sw95-98) completely abolishes both activities while the familial Alzheimer's disease mutation V96F significantly inhibits both activities. Reversion of residue 96 back to valine in the sw95-98 mutant rescues PS function, identifying V96 as the critical residue in this region. The TM1 mutants do not bind to an aspartyl protease transition state analog c-secretase inhibitor, indicating a conformational change induced by the mutations that abrogates catalytic activity. TM1 mutant PS1 molecules retain the ability to interact with c-secretase substrates and c-secretase complex members, although Nicastrin stability is decreased by the presence of these mutants. c-Secretase complexes that contain V96F mutant PS1 molecules display a partial loss of function for c-secretase that alters the ratio of amyloid-b peptide species produced, leading to the amyloid-b peptide aggregation that causes familial Alzheimer's disease.